LC-MS/MS profiling and toxicological evaluation of Argania spinosa extract: Acute and subacute studies in Swiss Albino mice with in vivo and in silico approaches

Abstract

Ethnopharmacological relevance: Argania spinosa (L.) Skeels, argan tree, scientifically known as (Arganier, أرݣان, ارڨان) and formerly referred to as Sideroxylon spinosum, is a tree endemic to southwestern Morocco. It is widely recognized for its numerous ethnobotanical and pharmacological properties, making it a valuable resource both ecologically and economically.

Aim of the study: The objective of the current study was to evaluate the acute and subacute toxicity profiles of Argania spinosa leaves extracts in mice, as well as the composition determined by LC-MS/MS, was employed to analyze and identify the compounds present in the extract. The primary compound in the studied extract, was selected for molecular docking analysis to explore its inhibitory mechanism against toxicity proteins.

Materials and methods: In the acute study, the extract was given to adult Swiss Albino mice via oral and intraperitoneal routes at doses ranging from 0 to 7 g/kg. In the subacute dose study, the extract was administered orally to adult mice at daily doses of 100, 250, and 500 mg/kg for 28 days. Body weight, along with selected biochemical and hematological parameters, was monitored. At the end of the treatment period, histological evaluations of the liver, kidney, and spleen were performed to identify any potential organ damage.

Results: Seventeen compounds were detected in the extract using LC-MS/MS analysis, with luteolin-7-O-glucoside, isorhamnetin-7-O-pentose, and quercetin-3-O-glucoside being the most prevalent. The predicted pharmacokinetic properties, indicate that the isolated compounds are well-absorbed, with a high human intestinal absorption. The acute toxicity evaluation revealed LD₅₀ values of 6 g/kg for oral administration and 4 g/kg for intraperitoneal administration of the extract. During the subacute toxicity assessment, no notable alterations in body weight or organ weights were observed. Similarly, no changes in hematological or biochemical parameters were noted. Microscopic examination of vital organs such as the liver, kidneys, and spleen revealed no significant lesions.

Conclusion: In conclusion, the leaves of Argania spinosa, revealing an interesting phytochemical composition. Furthermore, they exhibited no toxicity, making them a potential source of beneficial compounds for various applications, such as pharmaceuticals, and food products.

Keywords: Acute toxicity; Argania spinosa; LC–MS/MS; Molecular docking; Subacute toxicity.